BACKGROUND This study examined whether prazosin reduces alcohol drinking over the course of prolonged treatment and whether it blocks initiation of alcohol drinking in rats with a genetic predisposition toward high alcohol drinking, i.e, alcohol-preferring (P) rats. METHODS In study one, alcohol-experienced P rats that had been drinking alcohol 2 hrs/day for several months were treated daily with prazosin (0, 0.5, 1.0 or 2.0 mg/kg BW) for 7 weeks. In study two, alcohol-naïve P rats were treated daily with prazosin (0, 1.0 or 2.0 mg/kg BW) for two weeks prior to, or concomitantly with, initiation of alcohol access and throughout 3 weeks of alcohol availability. Prazosin treatment and alcohol access were then discontinued for 2 weeks followed by reinstatement of alcohol access without prazosin treatment for 4 weeks, followed by resumption of daily prazosin treatment (2.0 mg/kg BW) for 3 weeks. RESULTS Prazosin reduced alcohol drinking throughout 7 weeks of treatment in P rats accustomed to drinking alcohol. Following termination of prazosin treatment, alcohol drinking slowly returned to pretreatment baseline. Reduced alcohol intake was accompanied by increased water intake. In alcohol-naïve P rats, prazosin administration prior to the first opportunity to drink alcohol and throughout 3 weeks of alcohol access retarded acquisition of alcohol drinking and reduced the amount of alcohol consumed. When prazosin was administered concomitantly with the first opportunity to drink alcohol, it abolished acquisition of alcohol drinking. Discontinuation of prazosin treatment allowed expression of a genetic predisposition toward high alcohol drinking to gradually emerge. Prazosin retained the ability to reduce alcohol intake with repeated treatments. CONCLUSIONS Prazosin decreased alcohol drinking during prolonged treatment and may be useful for treating alcoholism and alcohol use disorders. Prazosin may also be useful for deterring initiation of drinking in individuals with a family history of alcoholism.

BACKGROUND Naltrexone (NTX) is under-utilized in clinical treatment settings because it’s efficacy is modest, it is not effective for all alcoholics and, when it is effective, a significant number of alcoholics fail to maintain initial treatment gains and subsequently relapse to heavy drinking. This has slowed acceptance of NTX by the treatment community and there is a clear need for additional treatments for alcoholism and alcohol use disorders. Given that NTX and prazosin can each reduce alcohol drinking in rats selectively bred for alcohol preference and high voluntary alcohol drinking (alcohol-preferring “P” rats), we tested whether a combination of NTX + prazosin is more effective in decreasing alcohol drinking than is either drug alone. METHODS P rats were given access to a 15% (v/v) alcohol solution for two hrs daily. Rats were fed NTX and prazosin, alone or in combination, prior to onset of the daily 2 hr alcohol access period for 4 weeks and the effect of drug treatment on alcohol and water intake was assessed. RESULTS During the first week of treatment neither a low dose of NTX, nor prazosin, was effective in decreasing alcohol intake when each drug was administered alone, but combining the two drugs in a single medication significantly reduced alcohol intake. The combination was as effective as was a higher dose of NTX. Using a low dose of NTX in combination with prazosin may reduce the potential for undesirable side effects early in treatment which, in turn, may improve patient compliance and result in a more successful outcome when NTX is used for treating alcoholism and alcohol use disorders. CONCLUSIONS Combining low dose NTX and prazosin in a single medication may be more useful than is either drug alone for treating both inpatient and outpatient alcoholics and heavy drinkers early in the treatment process.

BACKGROUND Many alcoholics and heavy drinkers undergo repeated cycles of alcohol abstinence followed by relapse to alcohol drinking; a pattern that contributes to escalated alcohol intake over time. In rodents, alcohol drinking that is interspersed with periods of alcohol deprivation (imposed abstinence) increases alcohol intake during reaccess to alcohol. This is termed the “alcohol deprivation effect” or “ADE” and is a model of alcohol relapse in humans. We have previously reported that prazosin reduces alcohol drinking during both brief and prolonged treatment in rats selectively bred for alcohol preference (“P” rats). This study explores whether prazosin prevents alcohol “relapse” in P rats, as reflected by a reduced or abolished ADE. METHODS Adult male P rats were given 24-hour access to food and water and scheduled access to alcohol (15% and 30% v/v solutions presented concurrently) for 2 hrs/day. After 5 weeks rats underwent imposed alcohol deprivation for 2 weeks, followed by alcohol reaccess for 2 weeks, and this pattern was repeated for a total of 3 cycles. Rats were injected with prazosin (0, 0.5, 1.0, or 2.0 mg/kg BW, IP) once a day for the first 5 days of each alcohol reaccess cycle. RESULTS Alcohol intake increased on the first day of each alcohol reaccess cycle, demonstrating the formation of an ADE. The ADE was short-lived, lasting only 1 day, during each of the three cycles. Prazosin, in all doses tested, prevented the expression of an ADE in all three alcohol reaccess cycles. CONCLUSIONS Prazosin decreases alcohol intake in P rats even in a situation that would be expected to increase alcohol drinking, namely following periods of alcohol deprivation. This suggests that prazosin may be effective in reducing alcohol relapse that often occurs during attempts to achieve permanent alcohol abstinence in treatment-seeking alcoholics and heavy drinkers.

Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death worldwide. Hepatocellular carcinoma commonly metastasizes to lungs, lymph nodes, and bone. Although HCC usually occurs in setting of chronic liver disease due to alcoholism or HBV/HCV infection, the incidence of HCC arising from nonalcoholic steatohepatitis is increasing. We present a very unusual initial presentation of occult HCC with peritoneal carcinomatosis secondary to liver rupture in a 70-year-old man with known nonalcoholic steatohepatitis–cirrhosis, best appreciated on FDG PET/CT. Our patient died a few days later. Tumor rupture is a rare but usually rapidly lethal complication of HCC.